Thursday, May 17, 2012

Nature Chemical Biology Contents: June 2012 Volume 8 Number 6, pp 495 - 596

Nature Chemical Biology


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TABLE OF CONTENTS

June 2012 Volume 8, Issue 6

Focus
Editorial
Commentary
Research Highlights
News and Views
Reviews
Articles
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Focus

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Metabolism in 3D
Metabolism is reemerging as a central topic in chemistry and biology, and chemical biologists are poised to improve our understanding of complex questions such as regulation, flux, and spatial organization. In this issue, we feature reviews and commentary outlining the recent advances and outstanding challenges in metabolism research.
Metabolism in 3D

Editorial

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Beyond blueprints p495
doi:10.1038/nchembio.997
Renewed interest in the biological significance and applied outcomes of metabolism is moving the field from static biochemical charts to multidimensional networks.
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Commentary

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Teaching the design principles of metabolism pp497 - 501
Joshua D Rabinowitz and Livia Vastag
doi:10.1038/nchembio.969
Learning metabolism inevitably involves memorizing pathways. The teacher's challenge is to motivate memorization and to help students progress beyond it. To this end, students should be taught a few fundamental chemical reaction mechanisms and how these are repeatedly used to achieve pathway goals. Pathway knowledge should then be reinforced through quantitative problems that emphasize the relevance of metabolism to bioengineering and medicine.
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Research Highlights

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Metabolic engineering: Assembling activity | RNA transport: An hnRNP ruler | Stem cells: Imatinib gets beta | Neurobiology: Smells like mitochondria | Chemical probes: Motor control | Metabolism: Lathosterone for longer life | Biosynthesis: Malonyl? Stet. | Cell biology: Peroxisomes come together

News and Views

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Structural biology: CrkL is not Crk-like pp504 - 505
Yoshihiro Kobashigawa and Fuyuhiko Inagaki
doi:10.1038/nchembio.963
Crk-like (CrkL) is a key signaling protein that mediates the leukemogenic activity of Bcr-Abl. Structural investigations show that the intramolecular assembly of CrkL is entirely distinct from that of CrkII, shedding light on how CrkL specifically mediates Bcr-Abl signaling.
Full Text | PDF
See also: Article by Jankowski et al.

Biosynthesis: Ringing in a new view pp505 - 507
Wendy L Kelly
doi:10.1038/nchembio.973
Heterocycles such as thiazoles are introduced into ribosomally synthesized peptide metabolites by post-translational modification. The enzyme that installs those rings has been identified, providing insight into heterocyclization biochemistry and the potential capabilities of an entire protein family.
Full Text | PDF
See also: Article by Dunbar et al.

Antisense therapeutics: New ways to nudge splicing pp507 - 508
Ian Eperon
doi:10.1038/nchembio.968
Duplexes formed between pre-mRNA and 2′-fluorinated oligonucleotides suppress nearby splice sites by recruiting double-stranded RNA-binding proteins.
Full Text | PDF
See also: Article by Rigo et al.

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Reviews

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Rethinking glycolysis: on the biochemical logic of metabolic pathways pp509 - 517
Arren Bar-Even, Avi Flamholz, Elad Noor and Ron Milo
doi:10.1038/nchembio.971
Abstract | Full Text | PDF

Engineering synthetic recursive pathways to generate non-natural small molecules pp518 - 526
Elizabeth A Felnagle, Asha Chaubey, Elizabeth L Noey, Kendall N Houk and James C Liao
doi:10.1038/nchembio.959
Abstract | Full Text | PDF

Natural strategies for the spatial optimization of metabolism in synthetic biology pp527 - 535
Christina M Agapakis, Patrick M Boyle and Pamela A Silver
doi:10.1038/nchembio.975
Abstract | Full Text | PDF

Systems metabolic engineering of microorganisms for natural and non-natural chemicals pp536 - 546
Jeong Wook Lee, Dokyun Na, Jong Myoung Park, Joungmin Lee, Sol Choi and Sang Yup Lee
doi:10.1038/nchembio.970
Abstract | Full Text | PDF

Articles

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Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling pp547 - 554
Mathew Sajish, Quansheng Zhou, Shuji Kishi, Delgado M Valdez Jr, Mili Kapoor, Min Guo, Sunhee Lee, Sunghoon Kim, Xiang-Lei Yang and Paul Schimmel
doi:10.1038/nchembio.937



Trp-tRNA synthetase (TrpRS) has a well-understood role in translation by facilitating aminoacylation of Trp-tRNAs. The discovery of a nuclear signaling role for TrpRS as a bridging protein for DNA-PK and PARP-1, resulting in p53 activation, explains a previously curious link between interferon-γ signaling and concomitant TrpRS overexpression.
Abstract | Full Text | PDF

Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing pp555 - 561
Frank Rigo, Yimin Hua, Seung J Chun, Thazha P Prakash, Adrian R Krainer and C Frank Bennett
doi:10.1038/nchembio.939



Antisense oligonucleotides (ASOs) are widely used to modulate gene expression through sequence-specific duplex formation with target RNAs. ASOs containing specific 2′-fluorine substitutions are shown to recruit ILF2/3 to pre-mRNA and induce exon skipping in cells and in mice.
Abstract | Full Text | PDF
See also: News and Views by Eperon

Ultrasensitive regulation of anapleurosis via allosteric activation of PEP carboxylase  pp562 - 568
Yi-Fan Xu, Daniel Amador-Noguez, Marshall Louis Reaves, Xiao-Jiang Feng and Joshua D Rabinowitz
doi:10.1038/nchembio.941



Bacteria must control their metabolism to quickly adapt to changing carbon sources. PEP carboxylase is now shown to be allosterically regulated by fructose-1,6-bisphosphate in an ultrasensitive manner, turning glycolysis on and off almost instantaneously in response to glucose availability.
Abstract | Full Text | PDF

YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations pp569 - 575
Kyle L Dunbar, Joel O Melby and Douglas A Mitchell
doi:10.1038/nchembio.944



Cyclodehydrations in thiazole/oxazole-modified microcin biosynthesis are known to require a multiprotein complex, but full details of the reaction were not clear. Substrate analogs and isotopic labeling now show the D protein, thought to serve a scaffolding function, catalyzes ring formation and uses ATP to activate the substrate.
Abstract | Full Text | PDF
See also: News and Views by Kelly

A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation pp576 - 582
Giovanna Bergamini, Kathryn Bell, Satoko Shimamura, Thilo Werner, Andrew Cansfield, Katrin Müller, Jessica Perrin, Christina Rau, Katie Ellard, Carsten Hopf, Carola Doce, Daniel Leggate, Raffaella Mangano, Toby Mathieson, Alison O'Mahony, Ivan Plavec, Faiza Rharbaoui, Friedrich Reinhard, Mikhail M Savitski, Nigel Ramsden, Emilio Hirsch, Gerard Drewes, Oliver Rausch, Marcus Bantscheff and Gitte Neubauer
doi:10.1038/nchembio.957



A chemoproteomic approach adapted for high-throughput screening leads to the identification of a selective PI3Kγ inhibitor. Application of this inhibitor in human and mouse cellular models reveals a role for PI3Kγ in TH17 cell differentiation.
Abstract | Full Text | PDF | Chemical compounds

Fluorescent castasterone reveals BRI1 signaling from the plasma membrane pp583 - 589
Niloufer G Irani, Simone Di Rubbo, Evelien Mylle, Jos Van den Begin, Joanna Schneider-Pizoń, Jaroslava Hniliková, Miroslav Šíša, Dieter Buyst, Josep Vilarrasa-Blasi, Anna-Mária Szatmári, Daniël Van Damme, Kiril Mishev, Mirela-Corina Codreanu, Ladislav Kohout, Miroslav Strnad, Ana I Caño-Delgado, Jiří Friml, Annemieke Madder and Eugenia Russinova
doi:10.1038/nchembio.958



Brassinosteroids (BRs) are plant growth hormones that bind the brassinosteroid receptor (BRI1) and activate its kinase domain. Exploration of BRI1-BR trafficking using a fluorescent brassinosteroid probe alongside chemical and genetic tools reveals that endocytosis pathways are essential for BR signaling attenuation and BRI1 turnover.
Abstract | Full Text | PDF | Chemical compounds

Domain organization differences explain Bcr-Abl's preference for CrkL over CrkII  pp590 - 596
Wojciech Jankowski, Tamjeed Saleh, Ming-Tao Pai, Ganapathy Sriram, Raymond B Birge and Charalampos G Kalodimos
doi:10.1038/nchembio.954



NMR structures of CrkL, an adaptor protein that mediates Bcr-Abl signaling in CML, reveal domain organization distinct from CrkII that allows constitutive interaction between CrkL and Abl kinase.
Abstract | Full Text | PDF
See also: News and Views by Kobashigawa & Inagaki

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